The conversion of glucose to fat in rat adipose tissue is limited by the tissue's ability to catabolize glucose to acetyl-CoA, through pathways which involve adenine mono- and di-nucleotides and are thus directly related to the tissue's energy metabolism. We have shown that the conversion of glucose to fat is an energy-yielding process (i.e., a process requiring ADP!). Thus it becomes possible to envision that increased ATP production through fatty acid oxidation, in situations where FFA levels are elevated, should inhibit lipogenesis by diminishing the ADP available for lipogenesis. The aim of the proposed studies is to elucidate the physiological role of FFA in the regulation of adipose tissue lipogenesis and, in particular to determine whether changes in FFA levels are responsible for the differences in tissue's response to insulin, in a manner consistent with the impairment of lipogenesis during periods of high fat metabolism (fasting, high fat diet, etc.). If the regulation of lipogenesis in rat adipose tissue can be understood, it would be a comparatively simple matter to test whether the same regulatory phenomenon are operative in human adipose tissue. Such studies are proposed using human adipose tissue obtained at surgery, including patients supported by parenteral hyperalimentation, when lipogenesis is particularly high, due to the large amounts of glucose infused and the absence of dietary fat. This may help to identify the mechanisms which under usual nutritional conditions serve to control adipose tissue lipogenesis in man.